RESEARCH OBJECTIVES: The sites on fibronectin which are responsible for its interaction with collagen, and the cell surface are being investigated with an overall objective of understanding how these interactions influence cell function. Fibronectin, also known as cell surface protein or LETS protein, is a glycoprotein which is synthesized by cells in culture, is deposited on the cell surface, and becomes involved in the elaboration of a connective tissue matrix. Various functions have been attributed to cellular fibronectin among which are: cell attachment, cell morphology and cell motility. The synthesis of fibronectin by transformed or malignant cells is considerably diminished and its deposition on the cell surface is seriously impaired. A study of how fibronectin can influence the cell surface properties of normal and transformed cells is clearly of relevance to the understanding of cell malignancy and transformation. Enzymatically derived fragments of fibronectin are being studied to determine the nature and location of the sites which are responsible for the biological functions of fibronectin. One such study is the attachment of cells to gelatin coated surfaces, a process which is mediated by both cellular and plasma fibronectin. We have identified a distinct region in fibronectin which binds to collagen or gelatin which is structurally and conformationallydistinct from the rest of the polypeptide thus constituting a functional domain within the molecule. Experiments are being done with fibronectin and its fragments to identify and locate the sites which interact with the cell surface. The specific polypeptide sequences in fibronectin which interact with collagen will be further investigated. The long term objectives of this proposal is to map the biologically active sites in fibronectin.